Congenital mesoblastic nephroma 50 years after its recognition: A narrative review

Congenital mesoblastic nephroma (CMN) is a rare pediatric renal tumor with low malignant potential that most commonly occurs early in infancy. Treatment strategies are based on the few published CMN series, while a significant number of CMN patients have been described in case reports. The aim of this narrative review was to create an up‐to‐date overview of the literature. Complete surgical removal is curative in most cases. The risk of treatment‐related mortality (both surgery‐ and chemotherapy‐related) is relatively high in the first weeks of life, indicating that these young patients deserve special attention with respect to timing and type of treatment

Evaluation of O2PLS in Omics data integration

Background: Rapid computational and technological developments made large amounts of omics data available in different biological levels. It is becoming clear that simultaneous data analysis methods are needed for better interpretation and understanding of the underlying systems biology. Different methods have been proposed for this task, among them Partial Least Squares (PLS) related methods. To also deal with orthogonal variation, systematic variation in the data unrelated to one another, we consider the Two-way Orthogonal PLS (O2PLS): an integrative data analysis method which is capable of modeling systematic variation, while providing more parsimonious models aiding interpretation. Results: A simulation study to assess the performance of O2PLS showed positive results in both low and higher dimensions. More noise (50 % of the data) only affected the systematic part estimates. A data analysis was conducted using data on metabolomics and transcriptomics from a large Finnish cohort (DILGOM). A previous sequential study, using the same data, showed significant correlations between the Lipo-Leukocyte (LL) module and lipoprotein metabolites. The O2PLS results were in agreement with these findings, identifying almost the same set of co-varying variables. Moreover, our integrative approach identified other associative genes and metabolites, while taking into account systematic variation in the data. Including orthogonal components enhanced overall fit, but the orthogonal variation was difficult to interpret. Conclusions: Simulations showed that the O2PLS estimates were close to the true parameters in both low and higher dimensions. In the presence of more noise (50 %), the orthogonal part estimates could not distinguish well between joint and unique variation. The joint estimates were not systematically affected. Simultaneous analysis with O2PLS on metabolome and transcriptome data showed that the LL module, together with VLDL and HDL metabolites, were important for the metabolomic and transcriptomic relation. This is in agreement with an earlier study. In addition more gene expression and metabolites are identified being important for the joint covariation

Characteristics and outcome of pediatric renal cell carcinoma patients registered in the International Society of Pediatric Oncology (SIOP) 93‐01, 2001 and UK‐IMPORT database: A report of the SIOP‐Renal Tumor Study Group

In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric Oncology‐Renal Tumor Study Group (SIOP‐RTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93‐01, 2001 and UK‐IMPORT databases, were included. Event‐free survival (EFS) and overall survival (OS) were analyzed using the Kaplan‐Meier method. Between 1993 and 2019, 122 pediatric patients with RCC were registered. Available detailed data (n = 111) revealed 56 localized, 30 regionally advanced, 25 metastatic and no bilateral cases. Histological classification according to World Health Organization 2004, including immunohistochemical and molecular testing for transcription factor E3 (TFE3) and/or EB (TFEB) translocation, was available for 65/122 patients. In this group, the most common histological subtypes were translocation type RCC (MiT‐RCC) (36/64, 56.3%), papillary type (19/64, 29.7%) and clear cell type (4/64, 6.3%). One histological subtype was not reported. In the remaining 57 patients, translocation testing could not be performed, or TFE‐cytogenetics and/or immunohistochemistry results were missing. In this group, the most common RCC histological subtypes were papillary type (21/47, 44.7%) and clear cell type (11/47, 23.4%). Ten histological subtypes were not reported. Estimated 5‐year (5y) EFS and 5y OS of the total group was 70.5% (95% CI = 61.7%‐80.6%) and 84.5% (95% CI = 77.5%‐92.2%), respectively. Estimated 5y OS for localized, regionally advanced, and metastatic disease was 96.8%, 92.3%, and 45.6%, respectively. In conclusion, the registered pediatric patients with RCC showed a reasonable outcome. Survival was substantially lower for patients with metastatic disease. This descriptive study stresses the importance of full, prospective registration including TFE‐testing

Estimation of metabolite networks with regard to a specific covariable: applications to plant and human data

In systems biology, where a main goal is acquiring knowledge of biological systems, one of the challenges is inferring biochemical interactions from different molecular entities such as metabolites. In this area, the metabolome possesses a unique place for reflecting “true exposure” by being sensitive to variation coming from genetics, time, and environmental stimuli. While influenced by many different reactions, often the research interest needs to be focused on variation coming from a certain source, i.e. a certain covariable Xm . Objective Here, we use network analysis methods to recover a set of metabolite relationships, by finding metabolites sharing a similar relation to Xm . Metabolite values are based on information coming from individuals’ Xm status which might interact with other covariables. Methods Alternative to using the original metabolite values, the total information is decomposed by utilizing a linear regression model and the part relevant to Xm is further used. For two datasets, two different network estimation methods are considered. The first is weighted gene co-expression network analysis based on correlation coefficients. The second method is graphical LASSO based on partial correlations. Results We observed that when using the parts related to the specific covariable of interest, resulting estimated networks display higher interconnectedness. Additionally, several groups of biologically associated metabolites (very large density lipoproteins, lipoproteins, etc.) were identified in the human data example. Conclusions This work demonstrates how information on the study design can be incorporated to estimate metabolite networks. As a result, sets of interconnected metabolites can be clustered together with respect to their relation to a covariable of interest

Tissue-Specific Transcriptomics of the Exotic Invasive Insect Pest Emerald Ash Borer (Agrilus planipennis)

BACKGROUND: The insect midgut and fat body represent major tissue interfaces that deal with several important physiological functions including digestion, detoxification and immune response. The emerald ash borer (Agrilus planipennis), is an exotic invasive insect pest that has killed millions of ash trees (Fraxinus spp.) primarily in the Midwestern United States and Ontario, Canada. However, despite its high impact status little knowledge exists for A. planipennis at the molecular level. METHODOLOGY AND PRINCIPAL FINDINGS: Newer-generation Roche-454 pyrosequencing was used to obtain 126,185 reads for the midgut and 240,848 reads for the fat body, which were assembled into 25,173 and 37,661 high quality expressed sequence tags (ESTs) for the midgut and the fat body of A. planipennis larvae, respectively. Among these ESTs, 36% of the midgut and 38% of the fat body sequences showed similarity to proteins in the GenBank nr database. A high number of the midgut sequences contained chitin-binding peritrophin (248)and trypsin (98) domains; while the fat body sequences showed high occurrence of cytochrome P450s (85) and protein kinase (123) domains. Further, the midgut transcriptome of A. planipennis revealed putative microbial transcripts encoding for cell-wall degrading enzymes such as polygalacturonases and endoglucanases. A significant number of SNPs (137 in midgut and 347 in fat body) and microsatellite loci (317 in midgut and 571 in fat body) were predicted in the A. planipennis transcripts. An initial assessment of cytochrome P450s belonging to various CYP clades revealed distinct expression patterns at the tissue level. CONCLUSIONS AND SIGNIFICANCE: To our knowledge this study is one of the first to illuminate tissue-specific gene expression in an invasive insect of high ecological and economic consequence. These findings will lay the foundation for future gene expression and functional studies in A. planipennis

Dynamic changes in human-gut microbiome in relation to a placebo-controlled anthelminthic trial in Indonesia

Background: Microbiome studies suggest the presence of an interaction between the human gut microbiome and soil-transmitted helminth. Upon deworming, a complex interaction between the anthelminthic drug, helminths and microbiome composition might occur. To dissect this, we analyse the changes that take place in the gut bacteria profiles in samples from a double blind placebo controlled trial conducted in an area endemic for soil transmitted helminths in Indonesia. Methods: Either placebo or albendazole were given every three months for a period of one and a half years. Helminth infection was assessed before and at 3 months after the last treatment round. In 150 subjects, the bacteria were profiled using the 454 pyrosequencing. Statistical analysis was performed cross-sectionally at pre-treatment to assess the effect of infection, and at post-treatment to determine the effect of infection and treatment on microbiome composition using the Dirichlet-multinomial regression model. Results: At a phylum level, at pre-treatment, no difference was seen in microbiome composition in terms of relative abundance between helminth-infected and uninfected subjects and at post-treatment, no differences were found in microbiome composition between albendazole and placebo group. However, in subjects who remained infected, there was a significant difference in the microbiome composition of those who had received albendazole and placebo. This difference was largely attributed to alteration of Bacteroidetes. Albendazole was more effective against Ascaris lumbricoides and hookworms but not against Trichuris trichiura, thus in those who remained infected after receiving albendazole, the helminth composition was dominated by T. trichiura. Discussion: We found that overall, albendazole does not affect the microbiome composition. However, there is an interaction between treatment and helminths as in subjects who received albendazole and remained infected there was a significant alteration in Bacteroidetes. This helminth-albendazole interaction needs to be studied further to fully grasp the complexity of the effect of deworming on the microbiome. Trial registration: ISRCTN Registy, ISRCTN83830814

Improving access to healthcare for paediatric sickle cell disease patients: a qualitative study on healthcare professionals' views

Background: In well-resourced countries, comprehensive care programs have increased life expectancy of patients with sickle cell disease, with almost all infants surviving into adulthood. However, families affected by sickle cell disease are more likely to be economically disenfranchised because of their racial or ethnic minority status. As every individual child has the right to the highest attainable standard of health under the United Nations Convention on the Rights of the Child, it is essential to identify both barriers and facilitators with regard to the delivery of adequate healthcare. Optimal healthcare accessibility will improve healthcare outcomes for children with sickle cell disease and their families. Healthcare professionals in the field of sickle cell care have first-hand experience of the barriers that patients encounter when it comes to effective care. We therefore hypothesised that these medical professionals have a clear picture of what is necessary to overcome these barriers and which facilitators will be most feasible. Therefore, this study aims to map best practises and lessons learnt in order to attain more optimal healthcare accessibility for paediatric patients with sickle cell disease and their families. Methods: Healthcare professionals working with young patients with sickle cell disease were recruited for semi-structured interviews. An interview guide was used to ensure the four healthcare accessibility dimensions were covered. The interviews were transcribed and coded. Based on field notes, initial codes were generated, to collate data (both barriers and solutions) to main themes (such as “transportation”, or “telecommunication”). Through ongoing thematic analysis, definitive themes were formulated and best practices were reported as recommendations. Quotations were selected to highlight or illustrate the themes and link the reported results to the empirical data. Results: In 2019, 22 healthcare professionals from five different university hospitals in the Netherlands were interviewed. Participants included (paediatric) haematologists, nurses and allied health professionals. Six themes emerged, all associated with best practices on topics related to the improvement of healthcare accessibility for children with sickle cell disease and their families. Firstly, the full reimbursement of invisible costs made by caregivers. Secondly, clustering of healthcare appointments on the same day to help patients seeing all required specialists without having to visit the hospital frequently. Thirdly, organisation of care according to shared care principles to deliver specialised services as close as possible to the patient’s home without compromising quality. Fourthly, optimising verbal and written communication methods with special consideration for families with language barriers, low literacy skills, or both. Fifthly, improving the use of eHealth services tailored to users’ health literacy skills, including accessible mobile telephone contact between healthcare professionals and caregivers of children with sickle cell disease. Finally, increasing knowledge and interest in sickle cell disease among key stakeholders and the public to ensure that preventive and acute healthcare measures are understood and safeguarded in all settings. Conclusion: This qualitative study describes the views of healthcare professionals on overcoming barriers of healthcare accessibility that arise from the intersecting vulnerabilities faced by patients with sickle cell disease and their families. The recommendations gathered in this report provide high-income countries with a practical resource to meet their obligations towards individual children under the United Nations Convention on the Rights of the Child